The Rakai Project, a collaboration between the Uganda Ministry of Health, and Makerere, Columbia and Johns Hopkins Universities, has conducted HIV/TD epidemiologic and behavioral research and randomized trials of HIV prevention of HIV prevention in rural Rakai District, Uganda since 1988. (The randomized trials addresses addressed STD control for HIV prevention and the treatment of chorioamnionitis to prevent mother-to-child (MTC) transmission). We currently have a representative cohort of 12,000 subjects aged 15-59 under surveillance in collaboration with the Walter Reed Army Institute of Research (WRAIR). The Rakai cohort provides a pluripotential population allowing us to address most HPTN agenda priorities for HIV prevention research either as a single site, or in multi-site studies to developed by HPTN. The HPTN priority agenda items that can be addressed include perinatal lactational MTC HIV transmission, microbicide trials, community- randomized STD control by a hybrid of presumptive and syndromic treatment in low HIV prevalence settings, behavioral interventions and antiretroviral therapy in discordant couples. We have demonstrated the ability to enroll subjects (90% in the general population, 95% in pregnant women), to obtain high compliance with provision of samples and acceptance of treatment (greater than or equal to 90%), and to retain subjects for prolonged periods of time (general population 80% follow up 30 months, pregnant women 95% postpartum follow up). We have laboratory and data management facilities, and experienced field personnel, and have established innovative methods of sample collection in the respondent's homes to maximize coverage and compliance. The population can readily be expanded to meet HPTN requirements, and selective recruitment can target priority subgroups such as high risk "core groups", pregnant women 95% postpartum follow up). We have laboratory and data management facilities, and experienced field personnel, and have established innovative methods of sample collection in the respondent's homes to maximize coverage and compliance. The population can readily be expanded to meet HPTN requirements, and selective recruitment can target priority subgroups such as high risk "core groups", pregnant and lactating women, or discordant couples, and we propose such expansion in the current application. We have support from the Minister of Health and relevant collaborators in-country (e.g., Ugandan PIs include the Dean of Medicine and Director of the Institute of Public Health, Makerere University), as well as in the US (e.g., Drs. Jackson and Quin who direct the HPTN Core Laboratory Facility). In summary, Rakai is the largest established population-based HIV/STD cohort in Africa and is ideally suited for HPTN agenda priorities.